Eli Lilly’s Obesity Drug Retatrutide Clears Advanced Diabetes Trial

Elie Lilly said Thursday that its next-generation obesity drug, retatrutide, has cleared its first late-stage trial in type 2 diabetes patients, helping them manage their blood sugar levels and lose weight.

The drug reduced hemoglobin A1c – a key measure of blood sugar levels – by 1.7% to 2% on average at different doses at 40 weeks compared to placebo, meeting the study’s primary goal. Patients started the trial with an HbA1c level between 7% and 9.5% and were not taking other diabetes medications.

Retatrutide also met the study’s second goal, helping patients receiving the highest dose lose an average of 16.8% of their weight, or 36.6 pounds, at 40 weeks, evaluating only patients who remained on treatment. Analyzing all participants, including those who stopped treatment, the highest dose of the drug helped patients lose 15.3% of their weight.

Patients with type 2 diabetes have historically had trouble losing weight, so Lilly is “very excited” to see that the drug has resulted in both a competitive lowering of blood sugar levels and significant weight loss, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.

The company is also “very pleased” with the relatively low discontinuation rates due to side effects, which amount to up to 5%, he added.

These are the second late-stage results to date on retatrutide, which works differently than existing injections and appears to be more effective, at least for weight loss. Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its blockbuster weight loss injection Zepbound and its next pill, orforglipron.

But Lilly has not yet sought approval of the drug for obesity or diabetes. The company plans to release results from seven additional phase three trials of the drug by the end of the year.

There are no comparative trials of retatrutide versus other medications, making it difficult to directly compare effectiveness.

Still, retatrutide’s A1C reduction doesn’t appear to be the greatest Lilly has seen in its portfolio: Zepbound’s highest dose lowered the measure by more than 2% at 40 weeks in two separate trials of diabetic patients.

But Custer said retatrutide’s A1C reduction is still “very, very strong” compared to other diabetes drugs that don’t target gut hormones.

He also said it would be important to have options in the area of ​​obesity and diabetes because “not everyone will be helped or satisfied with the same treatment.” The choice of which drug to take will depend on the “individualized tailoring of solutions and patients”, particularly at an early stage of their diabetes treatment, he added.

For example, Custer said patients who want to regulate their blood sugar might benefit from Zepbound or retatrutide. But if they’re looking to lose more weight, the latter might be a better option, he said.

In the two separate diabetes trials, Zepbound helped patients lose slightly less weight than retatrutide. In a study called SURPASS-2, the highest dose of Zepbound helped patients lose an average of 13.1% of their weight at 40 weeks. In the other study, SURPASS-1, the higher dose helped patients lose an average of 11% of their weight after 40 weeks.

The safety profile of Retatrutide was similar to other injectable medications for diabetes and obesity, primarily causing gastrointestinal side effects. Approximately 26.5% of patients receiving the highest dose experienced nausea, while approximately 22.8% and 17.6% experienced diarrhea and vomiting, respectively.

Low rates of patients have experienced dysesthesia, which is an unpleasant nervous sensation.

Dubbed the “triple G” drug, retatrutide works by mimicking three hunger-regulating hormones – GLP-1, GIP and glucagon – rather than just one or two like existing treatments. It appears to have more powerful effects on a person’s appetite and food satisfaction than other treatments.

Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk’s semaglutide, the active ingredient in Wegovy, only mimics GLP-1.

As Retatrutide gets closer to market, Novo races to catch up with Lilly. In March 2025, Novo said it agreed to pay up to $2 billion for the rights to an early experimental drug from Chinese pharmaceutical company United Laboratories International.

Novo’s recently acquired drug is an obvious potential competitor to retatrutide because it also uses a three-pronged approach to promote weight loss and regulate blood sugar levels. But development of Novo’s treatment is much earlier, meaning it will be several years before it reaches patients.